Medication non-adherence and self-inflicted violence behaviors among 185,800 patients with schizophrenia in the community: a 12-year cohort study

Background Despite the importance of medication adherence in treatment effectiveness, little is known about the association between medication non-adherence and self-inflicted violence behaviors. We aimed to assess whether medication non-adherence increased the risk of self-inflicted violence behaviors among schizophrenics in communities (hypothesis 1) and whether the dose–response relationship existed (hypothesis 2). Methods This 12-year cohort study in western China recruited 292,667 community-dwelling schizophrenics. The proportion of regular medication (PRM) was calculated by dividing the time of “regular adherence” by the total time of antipsychotic treatment during follow-up period as an indicator of medication adherence. For hypothesis 1, medication adherence was designated as a binary variable with a threshold of 0.8 (PRM); for hypothesis 2, medication adherence was specified as five-category and continuous variables, respectively. Inverse probability weighting and mixed effects Cox proportional hazards models were conducted for confounders control and survival analyses. Results One hundred eighty-five thousand eight hundred participants were eligible for the final analyses, with a mean age of 47.49 years (SD 14.55 years), of whom 53.6% were female. For hypothesis 1, the medication non-adherence group (PRM < 0.8) had a lower risk of suicide (HR, 0.527, 95% CI, 0.447–0.620), an increased risk of NSSI (HR, 1.229, 95% CI, 1.088–1.388), and non-significant risk of attempted suicide compared with adherence group (PRM ≥ 0.8). For hypothesis 2, the lowest medication adherence (PRM < 0.2) was associated with increased risks of suicide attempt (HR, 1.614, 95% CI, 1.412–1.845), NSSI (HR, 1.873, 95% CI, 1.649–2.126), and a decreased risk of suicide (HR, 0.593, 95% CI, 0.490–0.719). The other non-adherence groups had lower risks for all three self-inflicted violence behaviors. The associations between medication adherence in continuous-variable and three outcomes were consistent with the categorical medication adherence results. Conclusions Almost no medication taken as prescribed was associated with an increased risk of suicide attempt and NSSI. However, medication adherence did not appear to prevent completed suicide. Besides, patients with moderate adherence had a lower incidence of suicide attempt and NSSI. These findings highlight the need for a more detailed portrayal of medication adherence and the need to be vigilant for suicide intent in schizophrenics with good medication adherence who may be overlooked previously. Supplementary Information The online version contains supplementary material available at 10.1186/s12916-024-03354-7.

Table S13.Association between levels of medication adherence and self-inflicted violence behaviors (Re-define the PRM for hypothesis 1) Table S14.Association between levels of medication adherence and self-inflicted violence behaviors (Re-define the PRM for hypothesis 2) Table S15.E-value for quantifying unmeasured confounders Table S16.Sex-stratified association between 2 levels of medication adherence and self-inflicted violence behaviors during follow-up period (for hypothesis 1) Table S17.Association between levels of medication adherence and self-inflicted violence behaviors among male patients (for hypothesis 2) Table S18.Association between levels of medication adherence and self-inflicted violence behaviors among female patients (for hypothesis 2) Table S19.Urbanity-stratified association between 2 levels of medication adherence and self-inflicted violence behaviors during follow-up period (for hypothesis 1) Table S20.Association between levels of medication adherence and self-inflicted violence behaviors among rural patients (for hypothesis 2) Table S21.Association between levels of medication adherence and self-inflicted violence behaviors among urban patients (for hypothesis 2) Table S22.Age-stratified association between 2 levels of medication adherence and self-inflicted violence behaviors during follow-up period (for hypothesis 1) Table S23.Association between levels of medication adherence and self-inflicted violence behaviors among patients aged 10 to 24 (for hypothesis 2) Table S24.Association between levels of medication adherence and self-inflicted violence behaviors among patients aged 25 to 44 (for hypothesis 2) Table S25.Association between levels of medication adherence and self-inflicted violence behaviors among patients aged 45 to 59 (for hypothesis 2) Table S26.Association between levels of medication adherence and self-inflicted violence behaviors among patients aged ≥60 (for hypothesis 2) Table S27.Non-proportional hazards test for main and subgroup analyses Table S28.Comparison of characteristics between the individuals with missing values and the included sample

Non-linear association
We used Cox proportional hazards model to estimate time-to-event associations of PRM and the risk of self-inflicted violence behaviors during follow-up.We utilized linear models to estimate stabilized weights for PRM.To assess balance in the distributions of covariates for continuous exposure within weighted cohorts, we examined the Pearson correlation between each covariate and PRM.A correlation of 0.1 or lower was deemed indicative of ideal balance.
To evaluate potential non-linear associations, dose-response relationships were assessed by restricted cubic spline function with 4 knots [1] .Non-linear associations were tested using the Wald statistics.The analysis was done using the R package "rms".The individuals of missing information on exposure and covariates had a median follow-up of 3.02 years and a maximum follow-up of 12.21 years.

Table S2 . Group differences of the incidence of self-inflicted violence behaviors during follow-up
Results are expressed as frequency and incidence in each group.† χ 2 tests were conducted between medication adherence group and medication non-adherence group.

Table S22 . Age-stratified association between 2 levels of medication adherence and self-inflicted violence behaviors during follow-up period (for hypothesis 1)
.29) for suicide attempt, and 0.24(0.49)for NSSI.In patients aged ≥60, the variance (standard deviation) of the random effect of region was 0.08(0.28)for suicide, 0.23(0.48)for suicide attempt, and 0.47(0.68)for NSSI.‡ Truncation time for patients aged to 24. § Truncation time for patients aged to 44. ¶ Truncation time for patients aged to 59.